Galanthamine is an alkaloid with high pharmacological activity that primarily occurs in Amaryllidaceae-type plants. In particular, its action as a more selective acetylcholinesterase inhibitor and the thus associated application in the treatment of neurodegenerative diseases, such as Alzheimer's disease, are to be emphasized. The amounts isolated from the naturally occurring Caucasian snowdrop Galanthus woronoyi are not sufficient, however, to cover the requirement of a pharmaceutical raw material. Since the end of the 1960s, galanthamine syntheses have therefore been known that occasionally show long and uneconomical reaction routes with poor total yields, however.
According to WO-A-97/110777, a more economical route for the galanthamine synthesis is to be provided by a specific selection of bromine narwedine as a starting product since bromine narwedine is debrominated with palladium (II) acetate with the addition of triphenylphosphine. The racemic narwedine that is obtained contains about 700-800 ppm of palladium, however, which also cannot be separated after repeated treatment with activated carbon. Even in the case of additional reaction steps, such as the reduction of racemic narwedine, which is described according to WO-A-96/12692 of the applicant, palladium is further detected in the reaction end product despite repeated working-up.
Galanthamine or galanthamine derivatives, which have palladium in a measure of 700-800 ppm, are not suitable, however, for the production of pharmaceutical agents, such as agents for treating Alzheimer's disease, since undesirable side effects caused by the palladium radicals can occur in the organism. Consequently, boundary values at <5 ppm are normalized for the oral administration of pharmaceutical agents, see “Note for Guidance on Specification Limits for Residues of Metal Catalysts” CPMP/SWP/QWP/4446/00.
The object of the invention is therefore to indicate processes of the above-mentioned type with which the above-mentioned, normalized boundary values can be maintained.